Widespread epistasis among beneficial genetic variants revealed by high-throughput genome editing

ABSTRACT: Summary The phenotypic effect of any genetic variant can be altered by variation at other genomic loci. Known as epistasis, these genetic interactions shape the genotype-phenotype map of every species, yet their origins remain poorly understood. To investigate this, we employed high-throughput genome editing to measure the fitness effects of 1,826 naturally polymorphic variants in four strains of Saccharomyces cerevisiae. About 31% of variants affect fitness, of which 24% have strain-specific fitness effects indicative of epistasis. We found that beneficial variants are more likely to exhibit genetic interactions and that these interactions can be mediated by specific traits such as flocculation ability. This work suggests that adaptive evolution will often involve trade-offs where a variant is only beneficial in some genetic backgrounds, potentially explaining why many beneficial variants remain polymorphic. In sum, we provide a framework to understand the factors influencing epistasis with single-nucleotide resolution, revealing widespread epistasis among beneficial variants. Graphical abstract Highlights • We measured the fitness effects of 1,826 natural variants in four strains of yeast• Fitness effects of 24% of non-neutral variants are strain dependent (epistatic)• Beneficial variants are more likely to be epistatic than deleterious variants• Epistatic interactions can be mediated by intermediate traits such as flocculation Ang et al. measured the fitness effects of 1,826 naturally occurring genetic variants in four strains of yeast. They found that many of them depend on the genetic background, e.g., are beneficial in one strain but deleterious in another, and that beneficial variants show greater propensity to be strain dependent than deleterious mutations.

SUBMITTER: Ang R 

PROVIDER: S-EPMC10112194 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature